Abstract Chronic binge drinking represents a major health and safety problem in our country. The adverse effects of this excessive use are widespread in terms of loss of life, productivity, accidents and harm. Persons who are chronic, heavy alcohol drinkers (i.e., consume 5 or more drinks on a weekly or more frequent basis) incur greater consequences if they maintain hazardous drinking levels and are also at increased risk for progression to Alcohol Dependence compared with non heavy drinkers. The goal of the proposed renewal application is to build on findings from the first phase to further elucidate the factors associated with escalation and maintenance of excessive ethanol drinking. In the first award phase, we supported the hypothesis that heavy binge social drinkers are more sensitive to the positive and rewarding effects of alcohol during rising blood alcohol concentrations, and are also less sensitive to sedating effects and cortisol response to alcohol compared with light drinkers. Sensitivity to the stimulant-like effects and tolerance to sedative-like effects of alcohol were associated with greater frequency of binge drinking over the first two years after the baseline laboratory sessions. In this renewal application, we propose to recruit and test a second cohort of 100 HDs, to increase sample size to N=290 (204 heavy and 86 light drinkers). In Aim 1, we will examine the role of acute alcohol responses (stimulation, sedation, wanting, cortisol, performance measures, etc.) to future drinking behaviors over time. In Aim 2, we propose to re-examine alcohol response five years after the initial determination from the last award period in the first cohort of subjects. The data will discern whether alcohol responses vary over time, and in whom, and if alcohol drinking in the intervening period moderates the relationship between baseline and re-examination response. The study paradigm provides a unique translational focus on intensive laboratory data combined with long-term prospective follow-up. We will determine the relative contributions of sensitivity to stimulant-like alcohol effects, tolerance to sedative-like effects, and objective responses (cortisol, performance, heart rate, etc.) to future drinking patterns over time. Such information may have important impact on the early identification of at-risk drinkers and the factors underlying hazardous drinking practices to improve prevention, education, and early intervention efforts.